Eun-Mi Lee1, Dae-Yong Kim2, Ah-Young Kim1, Eun-Joo Lee1, Sang-Hyeob Kim2, Myeong-Mi Lee2, Soo-Eun Sung2, Jin-Kyu Park2, Kyu-Shik Jeong3. 1. College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Republic of Korea. 2. College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea. 3. College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: jeongks@knu.ac.kr.
Abstract
AIMS: Losartan, an angiotensin II type 1 receptor blocker, attenuates transforming growth factor-β (TGF-β) signaling, which inhibits myogenic regeneration. Although many researchers have demonstrated that losartan has anti-fibrotic and protective effects on cardiac and skeletal muscles, for long-term administration to treat dystrophic disorders, it is essential to demonstrate not only the therapeutic effects of losartan on muscles but also its effects on other organs and on blood biochemistry. MAIN METHODS: Mdx mice, an animal model of Duchenne muscular dystrophy (DMD), were fed losartan dissolved in tap water. After 44weeks, the skeletal (gastrocnemius), cardiac, and diaphragm muscles of mdx mice were removed. Tissue and blood samples were collected from all experimental animals. Effects of losartan on muscle regeneration, fibrosis, and blood enzymatic profiles were evaluated. KEY FINDINGS: In histopathological findings and serum biochemistry analyses, chronic losartan administration showed muscular protective effects and inhibited fibrosis in skeletal (gastrocnemius), cardiac, and diaphragmatic muscles. In addition, losartan had no effects on other solid organs. Interestingly, losartan had beneficial effects on serum HDL ratio. SIGNIFICANCE: This study demonstrates the therapeutic effects of losartan on muscles and its effects on other organs and on blood biochemistry. In conclusion, our results provide useful information for consideration of chronic losartan administration be as a treatment of DMD.
AIMS: Losartan, an angiotensin II type 1 receptor blocker, attenuates transforming growth factor-β (TGF-β) signaling, which inhibits myogenic regeneration. Although many researchers have demonstrated that losartan has anti-fibrotic and protective effects on cardiac and skeletal muscles, for long-term administration to treat dystrophic disorders, it is essential to demonstrate not only the therapeutic effects of losartan on muscles but also its effects on other organs and on blood biochemistry. MAIN METHODS: Mdx mice, an animal model of Duchenne muscular dystrophy (DMD), were fed losartan dissolved in tap water. After 44weeks, the skeletal (gastrocnemius), cardiac, and diaphragm muscles of mdx mice were removed. Tissue and blood samples were collected from all experimental animals. Effects of losartan on muscle regeneration, fibrosis, and blood enzymatic profiles were evaluated. KEY FINDINGS: In histopathological findings and serum biochemistry analyses, chronic losartan administration showed muscular protective effects and inhibited fibrosis in skeletal (gastrocnemius), cardiac, and diaphragmatic muscles. In addition, losartan had no effects on other solid organs. Interestingly, losartan had beneficial effects on serum HDL ratio. SIGNIFICANCE: This study demonstrates the therapeutic effects of losartan on muscles and its effects on other organs and on blood biochemistry. In conclusion, our results provide useful information for consideration of chronic losartan administration be as a treatment of DMD.
Authors: Sang-Oh Han; Alexina C Haynes; Songtao Li; Dennis M Abraham; Priya S Kishnani; Richard Steet; Dwight D Koeberl Journal: Mol Genet Metab Date: 2019-10-17 Impact factor: 4.797
Authors: Maria Laura Jorge Micheletto; Tulio de Almeida Hermes; Bruno Machado Bertassoli; Giuliana Petri; Matheus Moreira Perez; Fernando Luiz Affonso Fonseca; Alzira Alves de Siqueira Carvalho; David Feder Journal: Int J Exp Pathol Date: 2020-12-09 Impact factor: 1.925